Fluorescence imaging using cyanine dyes is a rapidly emerging field to support surgical navigation and provide real-time illumination of anatomic structures. Emissions in the 700-900 nm range may avoid interference from tissue auto-fluorescence and can penetrate approximately 1 cm of tissue, as described in Adams et al., “Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer” J Biomed Opt. 2007 12(2), 024017; and, Keereweer et al., “Optical Image-Guided Cancer Surgery: Challenges and Limitations” Clin Cancer Res. 2013 19(14), 3745-3754.
Another application of fluorescence imaging is for the real-time intra-operative imaging of the biliary anatomy, including the biliary duct and cystic duct. Current methods often use indocyanine green (ICG) dye by either intra-biliary injection or intravenous injection before surgery. However, studies have shown clear problems in using ICG dye. These include poor efficiency and kinetics of excretion into bile (Tanaka et al., “Real-time intraoperative assessment of the extrahepatic bile ducts in rats and pigs using invisible near-infrared fluorescent light” Surgery 2008 144(1) 39-48) and adverse reaction with the patient (Benya et al., “Adverse reactions to indocyanine green: a case report and a review of the literature” Cathet Cardiovasc Diagn. 1989 17(4) 231-233).
There exists a need for sensitive compositions and methods to detect and measure an internal target non-invasively. Specifically, there exists a need for improved, stable cyanine dyes to detect injuries to various organs that may occur during laparoscopic or robotic surgery. The present invention satisfies these and other needs.